siRNA MICROBICIDES FOR PREVENTING AND TREATING DISEASES

a technology of microbicides and microorganisms, applied in the direction of drug compositions, organic chemistry, genetic material ingredients, etc., can solve the problems of significant drop in the hiv infection rate and the individual's higher risk of contracting hiv

Inactive Publication Date: 2009-01-22
IMMUNE DISEASE INST INC +1
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  • Abstract
  • Description
  • Claims
  • Application Information

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Benefits of technology

[0008]In one embodiment, the siRNA is formulated with a pharmaceutically acceptable carrier to form a microbicidal composition that can treat or prevent viral infection by a virus noted above. Preferably, the viral infection is an STD. Preferably, the viral infection is med

Problems solved by technology

Moreover, prior infection with another STD, such as HSV 2, predisposes an individual to a higher risk of con

Method used

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  • siRNA MICROBICIDES FOR PREVENTING AND TREATING DISEASES
  • siRNA MICROBICIDES FOR PREVENTING AND TREATING DISEASES
  • siRNA MICROBICIDES FOR PREVENTING AND TREATING DISEASES

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Methods

[0101]Mice. BALB / c mice (5-8 weeks old) were from Taconic Farms; FVB.Cg-Tg (GFPU)5Nagy mice were from Jackson Laboratories (11). Mice subcutaneously injected with 2 mg medroxyprogesterone acetate (Sicor) 1 wk earlier were infected with 104 (˜2 LD50) HSV-2 strain 186 per vagina (21). siRNA (500 pmole) complexed with Oligofectamine (Invitrogen), prepared according to the manufacturer's protocol, was administered per vagina in a maximal volume of 12 ul in two regimens—2 hr before and 4 hr after HSV-2 infection or 1 and 2 hr after HSV-2 infection. Mice were examined daily for signs of HSV-2 graded by a 5-point scale (0, no signs of infection; 1, slight genital erythema and edema; 2, moderate genital inflammation; 3, purulent genital lesions; 4, hind limb paralysis; 5, death) (21). Viral shedding from the genital epithelium was determined by swabbing (Micropur swab, PurFybr Inc) the vaginal cavity on day 6 post-infection and titrating virus on Vero cells. In some cases, the vagina...

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Abstract

The invention provides a microbicidal composition comprising at least one siRNA. The siRNA is an RNA duplex made of one or two molecules. A portion of the siRNA is identical to a target sequence in an essential gene of a virus. The virus may be a herpesvirus, for example, HSV-1 or HSV-2. Preferably, the herpesvirus is HSV-2. The microbicidal composition further comprises a pharmaceutically acceptable carrier. Also included in the invention are methods to prevent and treat viral infections by administration of the microbicidal composition. Preferably, the microbicidal composition is administered transmucosally.

Description

CROSS-REFERENCE[0001]This application is an International Application, which claims priority benefit of U.S. Provisional Application Ser. No. 60 / 687,216, filed on Jun. 3, 2005, the content of which is relied upon and incorporated herein by reference in its entirety, and benefit priority under 35 U.S.C. §119(e).GOVERNMENT SUPPORT[0002]This invention was supported, in part, by National Institutes of Health (NIH) Grant No. R21 AI058695 and R01 AI057552. The government of the United States has certain rights to the invention.BACKGROUND OF THE INVENTION[0003]Two well known species of human disease-causing herpes simplex viruses are herpes simplex virus type 1 (HSV-1) and its close cousin, herpes simplex virus type 2 (HSV-2), collectively HSV. At the molecular level, HSV-1 and HSV-2 share approximately 50% of their DNA. Both types infect the body's mucosal surfaces, usually the mouth or genitals, and then establish latency in the nervous system. For both HSV-1 and HSV-2 infections, at lea...

Claims

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Application Information

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IPC IPC(8): A61K9/127A61K31/7105A61P31/00C12N5/06C12N15/113
CPCA61K48/00C12N2310/14C12N15/1133C12N15/1131A61P31/00A61P31/12A61P31/14A61P31/20A61P31/22
Inventor LIEBERMAN, JUDYPALLISER, DEBORAHKNIPE, DAVID
Owner IMMUNE DISEASE INST INC
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